Funds are requested to (i) purchase a Varian 400 MHz DirectDrive NMR system with SMS autosampler and (ii) replace a 14-year old Gemini 400 MHz NMR spectrometer with a second Varian 400 MHz DirectDrive console. The existing Oxford magnet on the Gemini 400 is still very serviceable and will be used with the new console. Tied into this upgrade of the NMR facilities is an upgrade of a Varian INOVA 500 to be compatible with the DirectDrive system. These new/upgraded spectrometers will support the analytical efforts of eight NIH-supported faculty members at Boston College. These instruments will have a very profound effect for researchers developing methods for the synthesis of natural products/drugs. Such projects routinely require the acquisition of many NMR spectra, both 1D and simple 2D experiments, to confirm intermediates as well as end products. The updated NMR facility will also allow B.C. chemists to more easily explore nuclei other than 1H and 13C. Of particular note, many more 31P and 19F spectra will be acquired and used in organometallic catalyst characterization, modified nucleic acid synthesis, synthetic phospholipids characterization, and diverse enzyme assays. The requested autosampler will enhance sample throughput since it will maximize the use of long blocks of time that are frequently underutilized on the current outdated spectrometers, and the new automation capabilities will dramatically reduce setup time between data acquisitions and sample changes. Other NIH- supported projects will also benefit from these instruments. 13C-selected 1H-NMR experiments will be used to monitor glucose metabolism in B lymphocytes as a way of exploring how glucose is split between glycolysis and pentose phosphates pathways, and to monitor the response of the tumor cell line U937 to synthetic variants of 3-deoxy-phosphatidylinositol molecules that are thought to target Akt1. PUBLIC HEALTH RELEVANCE: The research that will use this instrumentation has three basic goals: (1) development of novel synthetic methods to produce natural products and drugs applicable to a wide variety of human diseases, (2) screening and further development of drugs to target diabetes and tumors, and (3) exploring how specific mammalian cells respond to growth and death signals.